Neurotransmitter Changes in SSADH Deficiency During Development
Author Information
Author(s): Jansen Erwin EW, Struys Eduard, Jakobs Cornelis, Hager Elizabeth, Snead O Carter, Gibson K Michael
Primary Institution: VU Medical Center, Amsterdam, the Netherlands
Hypothesis
GABA might be significantly elevated in embryonic Aldh5a1-/- mice.
Conclusion
The study found early GABAergic alterations in Aldh5a1-/- mice, which may lead to a heightened excitatory state and predispose them to epilepsy.
Supporting Evidence
- GABA and DHHA were significantly elevated at all gestational ages in Aldh5a1-/- mice.
- GHB and D-2-HG increased linearly with gestational age.
- Correlative studies in human amniotic fluid from SSADH-deficient pregnancies revealed significantly increased GABA.
Takeaway
Mice with a specific genetic condition have too much of a brain chemical called GABA while they are still developing, which might make them more likely to have seizures later.
Methodology
Embryos were obtained from pregnant mice and metabolites were quantified using isotope dilution mass spectrometry.
Limitations
The study did not isolate neural tissue from embryos, which may limit the understanding of GABA's role in the brain specifically.
Participant Demographics
Mice (Aldh5a1+/+ and Aldh5a1-/-) were used in the study.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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